{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/path-similarity-analysis-a-method-for","title":"Path Similarity Analysis: a Method for Quantifying Macromolecular Pathways","arxiv_id":"1505.04807","date":"2015-10-23","proceeding":null,"authors":[],"abstract":"Diverse classes of proteins function through large-scale conformational\nchanges; sophisticated enhanced sampling methods have been proposed to generate\nthese macromolecular transition paths. As such paths are curves in a\nhigh-dimensional space, they have been difficult to compare quantitatively, a\nprerequisite to, for instance, assess the quality of different sampling\nalgorithms. The Path Similarity Analysis (PSA) approach alleviates these\ndifficulties by utilizing the full information in 3N-dimensional trajectories\nin configuration space. PSA employs the Hausdorff or Fr\\'echet path\nmetrics---adopted from computational geometry---enabling us to quantify path\n(dis)similarity, while the new concept of a Hausdorff-pair map permits the\nextraction of atomic-scale determinants responsible for path differences.\nCombined with clustering techniques, PSA facilitates the comparison of many\npaths, including collections of transition ensembles. We use the closed-to-open\ntransition of the enzyme adenylate kinase (AdK)---a commonly used testbed for\nthe assessment enhanced sampling algorithms---to examine multiple microsecond\nequilibrium molecular dynamics (MD) transitions of AdK in its substrate-free\nform alongside transition ensembles from the MD-based dynamic importance\nsampling (DIMS-MD) and targeted MD (TMD) methods, and a geometrical targeting\nalgorithm (FRODA). A Hausdorff pairs analysis of these ensembles revealed, for\ninstance, that differences in DIMS-MD and FRODA paths were mediated by a set of\nconserved salt bridges whose charge-charge interactions are fully modeled in\nDIMS-MD but not in FRODA. We also demonstrate how existing trajectory analysis\nmethods relying on pre-defined collective variables, such as native contacts or\ngeometric quantities, can be used synergistically with PSA, as well as the\napplication of PSA to more complex systems such as membrane transporter\nproteins.","url_abs":"http://arxiv.org/abs/1505.04807v2","url_pdf":"http://arxiv.org/pdf/1505.04807v2.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"path-similarity-analysis-a-method-for","repo_url":"https://github.com/MDAnalysis/mdanalysis","is_official":1,"mentioned_in_paper":0,"mentioned_in_github":0,"framework":"none","reach":null}],"tasks":[],"methods":[],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"atlas_url":null,"mcp":null,"developers":"https://syntology.ai/developers"},"arxiv_metadata":null,"syntology_extracted_results":null}